Abstract:The inhibitory potential of sulforaphane against cancer has been suggested for different types of cancer, including ovarian cancer. We examined whether this effect is mediated by mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS), important signaling molecules related to cell survival and proliferation, in ovarian cancer cells. Sulforaphane at a concentration of 10 μM effectively inhibited the growth of cancer cells. Use of specific inhibitors revealed that activation of MAPK pathways by… Show more
“…1A) was measured and compared with Sul (isothiocyanate), which is known to be a strong inducer of NQO1 [19]. Sul also effectively inhibited the growth of ovarian cancer cells in our previous study [18]. Cur (curcuminoid) and Res (stilbenoid) are natural phenols.…”
Section: Resultsmentioning
confidence: 99%
“…It is also possible that endogenous antioxidant enzymes (e.g., NQO1) are induced in response to increased intracellular ROS levels or alteration of the cellular redox state [24, 26]. Sul-induced inhibition of the growth of cancer cells has been shown to be related to Sul-induced oxidation that can be prevented by a thiol-reducing agent [18].Fig. 4Activation of mitogen-activated protein kinases (MAPKs) by food-derived polyphenols.…”
Section: Resultsmentioning
confidence: 99%
“…Western blot analysis was carried out as described previously [18] . Cells were lysed using radioimmunoprecipitation assay buffer (50 mM Tris HCl at pH 8.0, 5 mM EDTA, 150 mM NaCl, 1% NP40, 0.5% sodium deoxycholate, 0.1% SDS, 10 mM sodium fluoride, 1 mM sodium orthovanadate, and 1 mM β-glycerophosphate) supplemented with protease inhibitor cocktail (Sigma-Aldrich).…”
The use of plant polyphenols to prevent cancer has been studied extensively. However, recent findings regarding the cancer-promoting effects of some antioxidants have led to reservations regarding the therapeutic use of food-derived antioxidants including polyphenols. The aim of this study was to evaluate the therapeutic potential of food-derived polyphenols and their use and safety in cancer patients. The free-radical scavenging ability of sulforaphane and various food-derived polyphenols including curcumin, epigallocatechin gallate, epicatechin, pelargonidin, and resveratrol was compared with their growth inhibitory effect on ovarian cancer cells. Oxidative stress and/or antioxidant responses and anti-proliferative pathways were evaluated after administering sulforaphane and polyphenols at doses at which they have been shown to inhibit the growth of ovarian cancer cells. No correlation was observed between their ability to scavenge free radicals and their ability to inhibit the growth of ovarian cancer cells. With the exception of epigallocatechin gallate, all of the antioxidants that were tested at doses that inhibited cell growth significantly increased NAD(P)H quinone dehydrogenase I (NQO1) expression but induced cell cycle arrest and/or apoptotic signaling. Epigallocatechin gallate exhibited a higher free radical scavenging activity but did not induce NQO1 expression at either the mRNA or at the protein level. Treatment with polyphenols at physiological doses did not significantly alter the growth of ovarian cancer cells or NQO1 expression. Therefore, individual food-derived polyphenols appear to have different anti-cancer mechanisms. Their modes of action in relation to their chemical properties should be established, rather than collectively avoiding the use of these agents as antioxidants.
“…1A) was measured and compared with Sul (isothiocyanate), which is known to be a strong inducer of NQO1 [19]. Sul also effectively inhibited the growth of ovarian cancer cells in our previous study [18]. Cur (curcuminoid) and Res (stilbenoid) are natural phenols.…”
Section: Resultsmentioning
confidence: 99%
“…It is also possible that endogenous antioxidant enzymes (e.g., NQO1) are induced in response to increased intracellular ROS levels or alteration of the cellular redox state [24, 26]. Sul-induced inhibition of the growth of cancer cells has been shown to be related to Sul-induced oxidation that can be prevented by a thiol-reducing agent [18].Fig. 4Activation of mitogen-activated protein kinases (MAPKs) by food-derived polyphenols.…”
Section: Resultsmentioning
confidence: 99%
“…Western blot analysis was carried out as described previously [18] . Cells were lysed using radioimmunoprecipitation assay buffer (50 mM Tris HCl at pH 8.0, 5 mM EDTA, 150 mM NaCl, 1% NP40, 0.5% sodium deoxycholate, 0.1% SDS, 10 mM sodium fluoride, 1 mM sodium orthovanadate, and 1 mM β-glycerophosphate) supplemented with protease inhibitor cocktail (Sigma-Aldrich).…”
The use of plant polyphenols to prevent cancer has been studied extensively. However, recent findings regarding the cancer-promoting effects of some antioxidants have led to reservations regarding the therapeutic use of food-derived antioxidants including polyphenols. The aim of this study was to evaluate the therapeutic potential of food-derived polyphenols and their use and safety in cancer patients. The free-radical scavenging ability of sulforaphane and various food-derived polyphenols including curcumin, epigallocatechin gallate, epicatechin, pelargonidin, and resveratrol was compared with their growth inhibitory effect on ovarian cancer cells. Oxidative stress and/or antioxidant responses and anti-proliferative pathways were evaluated after administering sulforaphane and polyphenols at doses at which they have been shown to inhibit the growth of ovarian cancer cells. No correlation was observed between their ability to scavenge free radicals and their ability to inhibit the growth of ovarian cancer cells. With the exception of epigallocatechin gallate, all of the antioxidants that were tested at doses that inhibited cell growth significantly increased NAD(P)H quinone dehydrogenase I (NQO1) expression but induced cell cycle arrest and/or apoptotic signaling. Epigallocatechin gallate exhibited a higher free radical scavenging activity but did not induce NQO1 expression at either the mRNA or at the protein level. Treatment with polyphenols at physiological doses did not significantly alter the growth of ovarian cancer cells or NQO1 expression. Therefore, individual food-derived polyphenols appear to have different anti-cancer mechanisms. Their modes of action in relation to their chemical properties should be established, rather than collectively avoiding the use of these agents as antioxidants.
“…Additionally, SFN induced apoptosis and increased S phase cells and G1 arrest in MDAH-2774 cells. Kim et al [ 179 ] reported the effect of SFN on cell growth at 72 h in OVCAR3, OVCAR4, OVCAR5, and SKOV3 cell lines and found that SFN was effective at inhibiting cancer cell growth via activation of p38 and ERK. In a separate study, SFN treatment over a 24 h period induced apoptosis in SKOV3 and A2780 ovarian cancer cell lines.…”
Section: Sulforaphane In Cancer Prevention and Interventionmentioning
There is substantial and promising evidence on the health benefits of consuming broccoli and other cruciferous vegetables. The most important compound in broccoli, glucoraphanin, is metabolized to SFN by the thioglucosidase enzyme myrosinase. SFN is the major mediator of the health benefits that have been recognized for broccoli consumption. SFN represents a phytochemical of high interest as it may be useful in preventing the occurrence and/or mitigating the progression of cancer. Although several prior publications provide an excellent overview of the effect of SFN in cancer, these reports represent narrative reviews that focused mainly on SFN’s source, biosynthesis, and mechanisms of action in modulating specific pathways involved in cancer without a comprehensive review of SFN’s role or value for prevention of various human malignancies. This review evaluates the most recent state of knowledge concerning SFN’s efficacy in preventing or reversing a variety of neoplasms. In this work, we have analyzed published reports based on in vitro, in vivo, and clinical studies to determine SFN’s potential as a chemopreventive agent. Furthermore, we have discussed the current limitations and challenges associated with SFN research and suggested future research directions before broccoli-derived products, especially SFN, can be used for human cancer prevention and intervention.
“…Increasing evidence has shown that the isothiocyanate (ITC) compound sulforaphane (SFN) and its analogs have great potential to prevent the growth of various tumor cells, including those in lung cancer [17], skin cancer [18], colon cancer [19], breast cancer [20], and ovarian cancer [21]. Pharmacokinetic studies in both humans and animals have shown that SFN is metabolized via the mercapturic acid pathway, producing predominantly cysteinylglycine (SFN-CG), cysteine (SFN-Cys), and N-acetyl-cysteine conjugates (SFN-NAC), which are excreted in the urine [22].…”
Background/Aims: Sulforaphane-N-acetyl-cysteine (SFN-NAC) is a sulforaphane (SFN) metabolite with a longer half-life and better blood–brain barrier permeability than those of SFN. Previous studies have found that SFN-NAC can act via ERK to destroy microtubules and inhibit cell growth in lung cancer cells. However, the underlying mechanisms are unclear, and it is unknown whether SFN-NAC can inhibit the growth of glioma. Here, we have demonstrated for the first time that SFN-NAC activates autophagy-mediated downregulation of α-tubulin expression via the ERK pathway. Methods: U87MG and U373MG cells, two widely used glioma cell lines, were utilized in this study. Apoptosis assay, western blot analysis, co-immunoprecipitation, immunostaining, and electron microscopy were used to analyze the effect of SFN-NAC on α-tubulin and its interaction with microtube-associated protein 1 light-chain 3 (LC3). Results: SFN-NAC induced cell-cycle arrest in the G2/M phase and dose-dependently induced intracellular ERK activation, autophagy, and α-tubulin downregulation. These SFN-NAC-induced effects were reversed by inhibiting the ERK pathway with its inhibitor PD98059. U87MG and U373MG cells were transfected with LC3 small interfering RNA, and the subsequent inhibition of autophagy reversed the downregulation of α-tubulin by SFN-NAC. Furthermore, co-immunoprecipitation experiments and confocal microscopy confirmed that SFN-NAC promotes the binding of LC3 with α-tubulin in the cytoplasm. Cell viability experiments demonstrate that SFN-NAC inhibits the growth of U87MG and U373MG cell colonies. Conclusion: These findings suggest that SFN-NAC is a novel potential anti-glioma agent.
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